The present invention relates to methods and compositions for treating and preventing hearing loss.
A major cause of acquired hearing loss is loud noise. Exposure to harmful noise levels is common in the workplace. The National Institute for Occupational Safety and Health estimates that about 30 million workers in the United States encounter hazardous levels of noise. (Franks et al. (1996) Preventing Occupational Hearing Lossxe2x80x94A Practical Guide, DHHA (NIOSH) Publication No. 96-110, p.1). These levels are encountered in, for example, construction, mining, agriculture, manufacturing and utilities, transportation, and in the military. The incidence of noise associated hearing loss continues to increase in spite of efforts to regulate job related noise exposure, and to improve the use of hearing protective devices such as ear muffs and ear plugs.
Another cause of hearing loss is exposure to ototoxic drugs such as cisplatin and aminoglycoside antibiotics. Accordingly, there is a need for methods and compositions to prevent or treat hearing loss.
In one aspect the present invention provides methods for ameliorating hearing loss, the methods each comprising the step of administering to a subject an amount of an otoprotectant composition that is effective to ameliorate hearing loss. The otoprotective composition includes at least one of the otoprotectants disclosed herein. In some embodiments, the otoprotective composition comprises a pharmaceutically effective amount of at least one glutathione peroxidase mimic (e.g., a composition comprising ebselen). In some embodiments, the otoprotective composition comprises a pharmaceutically effective amount of (a) at least one glutathione peroxidase mimic and (b) at least one xanthine oxidase inhibitor (e.g., a composition comprising ebselen and allopurinol). In some embodiments, the otoprotective composition comprises a pharmaceutically effective amount of (a) at least one glutathione peroxidase mimic and (b) at least one glutathione or glutathione precursor (e.g., a composition comprising ebselen and N-acetyl-cysteine). In some embodiments, the otoprotective composition comprises a pharmaceutically effective amount of (a) at least one xanthine oxidase inhibitor and (b) at least one glutathione or glutathione precursor (e.g., a composition comprising allopurinol and N-acetyl-cysteine). In some embodiments, the otoprotective composition comprises a pharmaceutically effective amount of (a) at least one glutathione peroxidase mimic, (b) at least one xanthine oxidase inhibitor, and (c) at least one glutathione or glutathione precursor (e.g., a composition comprising ebselen, allopurinol, and N-acetyl-cysteine).
Another aspect of the present invention provides otoprotective compositions useful for ameliorating hearing loss. The otoprotective compositions include at least one of the otoprotectants disclosed herein. In some embodiments, the otoprotective compositions comprise at least one glutathione peroxidase mimic. In some embodiments, the otoprotective compositions comprise at least one glutathione peroxidase mimic and at least one xanthine oxidase inhibitor. In some embodiments, the otoprotective compositions comprise at least one glutathione peroxidase mimic and at least one glutathione or glutathione precursor. In some embodiments, the otoprotective compositions comprise at least one xanthine oxidase inhibitor and at least one glutathione or glutathione precursor. In some embodiments, the otoprotective compositions comprise at least one glutathione peroxidase mimic, at least one xanthine oxidase inhibitor, and at least one glutathione or glutathione precursor.